Water → (2S)-2-Cyclopentyl-2-hydroxy-2-thien-2-ylacetic Acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester

HRID 1360616Notes

Reaction equation

HRID 1360616 reaction equation
[CH:1]1([C@@:6]([OH:15])([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[C:7]([OH:9])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.O[C@H:29]1[CH:34]2[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]2)[CH2:30]1.O>CN(C=O)C>[N:31]12[CH2:36][CH2:35][CH:34]([CH2:33][CH2:32]1)[C@H:29]([O:8][C:7](=[O:9])[C@:6]([CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)([OH:15])[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)[CH2:30]2

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 7364113-Quinuclidinol, (+)-HCID 66608566HCID 66608566, compound

Product 1

HCID 66959269(2S)-2-Cyclopentyl-2-hydroxy-2-thien-2-ylacetic Acid (3S)-1-azabicyclo[2.2.2]oct-3-yl esterYield 47.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

510 mg (0.00225 mol) of (2S)-2-Cyclopentyl-2-hydroxy-2-thien-2-ylacetic acid (obtained by hydrolysis of Intermediate I-15a) were dissolved in 7 ml of DMF. This solution was stirred at room temperature and 638 mg (0.00393 mol) of 1,1′-carbonyldiimidazol were added in several portions. After 4.5 h the reaction mixture was cooled to 0° C. and 315 mg (0.00248 mol) of (3S)-3-hydroxy-1-azabicyclo[2.2.2]octane and 83 mg (0.0021 mol) of HNa (60% dispersion in mineral oil) were added thereto. After stirring 112 h at room temperature the reaction mixture was treated with water and extracted three times with diethyl ether. The organic layers were combined, washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography (eluent CHCl3/MeOH 15:1) to obtain 360 mg (47.6%) of the title product as an oil, structure confirmed by 1H-RMN.

Workup

  1. temperatureAfter 4.5 h the reaction mixture was cooled to 0° C.
  2. stirringAfter stirring 112 h at room temperature the reaction mixture
  3. extractionextracted three times with diethyl ether
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified by silica gel column chromatography (eluent CHCl3/MeOH 15:1)

Sources & evidence

ORD record
ord-26451d333d9742ee8dd600815774ee75
Source dataset
uspto-grants-2011_02
Patent number
US07879874B2

Reaction notes

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